Editorial: The toxicology of cannabis and cannabis-based products

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Abstract
Cannabis and cannabinoids invite us to reflect on an enduring tension between human intention and biological consequence: the pursuit of relief, pleasure, or new experiences may carry risks that extend beyond what is sought or anticipated. Acute exposure to tetrahydrocannabinol (THC)-containing cannabis can impair attention, memory, coordination, and decision-making, and may cause anxiety, confusion, paranoia, and cardiovascular effects. Frequent cannabis use has also been associated with an increased risk of cannabis use disorder and adverse cognitive and mental health outcomes, although the strength of evidence and causal relationships vary across outcomes (Hoch et al. 2025;National Academies of Sciences, Engineering, and Medicine, 2024).Cannabis use patterns and the availability of cannabis-based products have diversified considerably in recent years, with the market now encompassing products with varying cannabinoid compositions and concentrations, including dried cannabis, extracts and concentrates, edibles, vaping formulations, and products containing individual cannabinoids such as THC and cannabidiol (CBD) (National Academies of Sciences, Engineering, and Medicine, 2024; Tassone et al. 2023). This diversification introduces distinct exposure scenarios, in which formulation, route of administration, dose, frequency of use, and individual susceptibility can influence cannabinoid disposition and effects (Lucas et al. 2018). The importance of formulation and dosing conditions is illustrated by the variability of CBD pharmacokinetics (Moazen-Zadeh et al. 2024).THC-containing edible products pose particular risks because their delayed onset can encourage repeated dosing before effects become apparent, while unintentional ingestion by children can cause severe intoxication (National Academies of Sciences, Engineering, and Medicine, 2024).Despite advances in understanding cannabis toxicology, important gaps remain regarding repeated and long-term exposure, the effects of complex mixtures, and the contribution of contaminants and degradation products to overall toxicity. Addressing these gaps requires research integrating mechanistic toxicology, exposure assessment, and clinical observations to support informed clinical decisions and regulatory risk assessment.The present Research Topic brings together 11 complementary contributions, including original research, reviews, case reports, and a perspective, spanning molecular and cellular mechanisms, pediatric toxicity, cannabinoid hyperemesis, cannabinoid and alcohol co-exposure, inhalation toxicology, product chemistry, and regulatory risk assessment. These contributions are summarized below.This article collection moves beyond a THC-centered view of cannabis toxicity. The review by Teixeira provides an overview of phytocannabinoids and synthetic cannabinoids in the context of recreational use and potential therapeutic applications, highlighting the diversity of their structures, pharmacological targets, and adverse effects. This review provides a conceptual framework for the experimental studies in the collection.Consumer use of CBD has expanded, despite uncertainties concerning repeated exposure and long-term effects (Silva and Carvalho 2022). In this context, Camacho et al. compared purified CBD with a CBD-rich hemp extract at matched CBD concentrations in 0.5 % sesame-oil emulsions, assessing development and reproduction in Caenorhabditis elegans. Juveniles were more sensitive than adults, with reduced body size and developmental delays that persisted after early exposure ended.Continuous exposure beginning at parental reproductive maturity also reduced progeny output. The extract generally produced less pronounced effects than purified CBD.These findings identify hazards in this model; high internal CBD concentrations and interspecies differences preclude direct inference about risk at human consumer or therapeutic doses.Wong et al. compared chemically synthesized and plant-derived CBD, observing similar responses in the in vitro genotoxicity, hepatotoxicity, and cytochrome P450 activity assays examined. In a separate pharmacokinetic study, one synthesized CBD preparation was administered orally to male Sprague-Dawley rats at 26.5 mg/kg/day for 21 days. Repeated dosing increased systemic exposure, with preferential retention in adipose tissue and mesenteric lymph nodes. These findings support comparability for the in vitro endpoints assessed and the importance of repeated-dose toxicokinetics, but do not establish equivalent in vivo behavior or long-term safety across CBD sources.Cannabis toxicology also requires consideration of constituents other than cannabinoids. The mini review by Russo and Whiteley addresses cannabinoid hyperemesis syndrome (CHS), which is associated with prolonged, frequent use of THC-containing cannabis and has also been reported following exposure to other CB1 receptor agonists. The authors discuss proposed mechanisms, diagnostic challenges relative to cyclic vomiting syndrome, and hypotheses concerning pesticide contamination. They also consider non- Masilamani et al. describe a case report from a 7-year-old child who developed asystole lasting more than 15 seconds with apnea approximately seven hours after a reported ingestion of 75 mg of Δ⁸-THC in gummies (approximately 3 mg/kg). The child had already developed lethargy three to four hours after ingestion, despite initially stable vital signs. This case highlights the possibility of delayed severe events following substantial edible exposures, but does not establish a universal observation period.Together, these pediatric contributions support child-resistant packaging, safe storage, clinical recognition, and observation tailored to dose, symptoms, co-exposures, and clinical course.The Perspective by Achuthan et al. provides a regulatory dimension to the collection.Using Canadian data on regulated dried cannabis and cannabis vaping products,...

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